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  1. Fulltext Immune Biomarkers in Blood from Sarcoma Patients: A Pilot Study
    Munisamy S, Radhakrishnan AK, Ramdas P, Samuel PJ, Singh VA
    Curr Oncol, 2022 Aug 05;29(8):5585-5603.
    PMID: 36005179 DOI: 10.3390/curroncol29080441
    The main role of the host immune system is to identify and eliminate cancer cells, which is a complex process, but it is not a fail-safe mechanism. Many sarcoma patients succumb to this disease despite treatments rendered. The aim of this pilot study was to compare the levels of CD4+ T-cells, T-regulatory (Treg) cells, and cytokines such as tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-17A (IL-17A), and transforming growth factor-beta-1 (TGF-β1) in peripheral blood leukocytes of sarcoma patients and healthy controls. For gene expression studies, total ribonucleic acid (RNA) was extracted from peripheral blood leukocytes and genes that were differentially regulated in peripheral blood leukocytes of sarcoma patients compared with healthy controls were determined using a commercial T-helper cell differentiation quantitative polymerase chain reaction (qPCR) array. Flow cytometer analysis was performed on blood samples from 26 sarcoma patients and 10 healthy controls to identify the levels of CD4+ T-cells and T-reg cells. The level of cytokines in plasma and culture supernatant were quantified using commercial enzyme-linked immunosorbent assay (ELISA) kits. A marked reduction in the percentage of CD4+ T-cells (p = 0.037) and levels of TNF-α (p = 0.004) and IFN-γ (0.010) was observed in sarcoma patients. Gene expression analysis showed five genes (homeobox A10 (HOXA10), GATA binding protein 3 (GATA3), prostaglandin D2 receptor 2 (PTGDR2), thymocyte selection associated high mobility group box (TOX), and C-C motif chemokine receptor 3 (CCR3)) were dysregulated (p < 0.05) in sarcoma patients. This study suggests that T-helper-1 immune responses are reduced in sarcoma patients.
    Matched MeSH terms: Interferon-gamma/genetics; Interferon-gamma/metabolism
  2. Fulltext First evaluation of the performance of portable IGRA, QIAreach® QuantiFERON®-TB in intermediate TB incidence setting
    Aziz ZA, Noordin NM, Wan Mohd WM, Kasim MA
    PLoS One, 2023;18(2):e0279882.
    PMID: 36763619 DOI: 10.1371/journal.pone.0279882
    Diagnosis and treatment of tuberculosis infection (TBI) are the core elements of tuberculosis elimination. Interferon gamma release assays have advantages over the tuberculin skin test, although their implementation in low-resource settings is challenging. The performance of a novel digital lateral flow assay QIAreach® QuantiFERON®-TB (QIAreach QFT) against the QuantiFERON®-TB Gold Plus (QFT-Plus) assay was evaluated in an intermediate incidence setting (Malaysia) according to the manufacturer's instructions. Individuals aged 4-82 years, who were candidates for TB infection screening for contact investigation were prospectively recruited. On 196 samples, the QIAreach-QFT showed a positive percent agreement (sensitivity) was 96.5% (CI 87.9-99.6%), a negative percent agreement (specificity) 94.2% (CI 88.4% to 97.6%) and an overall percentage of agreement was 94.9% (95% CI 90.6-97.6%) with a Cohen's κ of 0,88. Out of 196, 5.6% (11/196) samples gave an error result on QIAreach-QFT and 4.1% (8/196) samples gave indeterminate result on QFT-plus. The TTR for QIAreach QFT positive samples varied from 210-1200 seconds (20 min) and significantly correlated with IFN-γ level of QFT-Plus. QIAreach QFT could be considered an accurate and reliable point-of-need test to diagnose TB infection helping to achieve the WHO End TB programme goals even in decentralised settings where laboratory expertise and infrastructure may be limited.
    Matched MeSH terms: Interferon-gamma Release Tests
  3. Release of pro-inflammatory cytokines TNF-α, IFN-γ and IL-6 by Burkholderia pseudomallei- stimulated peripheral blood mononucleocytes of acute myeloid leukemia patients
    Zulpa AK, Barathan M, Iyadorai T, Chandramathi S, Vellasamy KM, Vadivelu J, et al.
    Trop Biomed, 2021 Jun 01;38(2):180-185.
    PMID: 34172708 DOI: 10.47665/tb.38.2.055
    Acute myeloid leukemia (AML) is a malignant disease progressed from abnormal production of immature myeloid cells, which is often associated with concurrent infections after diagnosis. It was widely established that infections are the major contributors to mortality in this group due to the prevalency of neutropenia. Gram-negative Burkholderia pseudomallei is the causative agent of melioidosis. This disease had been reported in several neutropenic cancer patients undergoing chemotherapy resulting in severe clinical presentations and high mortalities which is in need of critical attention. Studies show that cytokines are important mediators of melioidosis progression and low neutrophil counts are associated with progression of its severity. However, to date, there are no reports on cytokine production in neutropenic cancer patients who are prone to melioidosis. Hence, here we assessed the cytokine production in neutropenic AML patients by introducing B. pseudomallei to their peripheral blood mononuclear cell (PBMC) culture in vitro. We observed that inflammatory response related cytokines namely TNF-α, IFN-γ IL-6 and IL-10 were highly circulated in infected PBMCs suggesting that these cytokines may play important roles in the progression of severity in melioidosis infected neutropenic patients.
    Matched MeSH terms: Interferon-gamma/blood*
  4. Fulltext Supplementation with natural forms of vitamin E augments antigen-specific TH1-type immune response to tetanus toxoid
    Radhakrishnan AK, Mahalingam D, Selvaduray KR, Nesaretnam K
    Biomed Res Int, 2013;2013:782067.
    PMID: 23936847 DOI: 10.1155/2013/782067
    This study compared the ability of three forms of vitamin E [tocotrienol-rich fraction (TRF), alpha-tocopherol (α-T), and delta-tocotrienol (δ-T3)] to enhance immune response to tetanus toxoid (TT) immunisation in a mouse model. Twenty BALB/c mice were divided into four groups of five mice each. The mice were fed with the different forms of vitamin E (1 mg) or vehicle daily for two weeks before they were given the TT vaccine [4 Lf] intramuscularly (i.m.). Booster vaccinations were given on days 28 and 42. Serum was collected (days 0, 28, and 56) to quantify anti-TT levels. At autopsy, splenocytes harvested were cultured with TT or mitogens. The production of anti-TT antibodies was augmented (P < 0.05) in mice that were fed with δ-T3 or TRF compared to controls. The production of IFN-γ and IL-4 by splenocytes from the vitamin E treated mice was significantly (P < 0.05) higher than that from controls. The IFN-γ production was the highest in animals supplemented with δ-T3 followed by TRF and finally α-T. Production of TNF-α was suppressed in the vitamin E treated group compared to vehicle-supplemented controls. Supplementation with δ-T3 or TRF can enhance immune response to TT immunisation and production of cytokines that promote cell-mediated (TH1) immune response.
    Matched MeSH terms: Interferon-gamma/biosynthesis; Interferon-gamma/immunology
  5. A potential marker in brucellosis, long non coding RNA IFNG-AS1
    Gheitasi R, Jourghasemi S, Pakzad I, Hosseinpour Sarmadi V, Samieipour Y, Sekawi Z, et al.
    Mol Biol Rep, 2019 Dec;46(6):6495-6500.
    PMID: 31595441 DOI: 10.1007/s11033-019-05095-w
    Brucellosis is the most common bacterial zoonotic infection. This pathogen may survive and sustain in host. The aim of this study is to define relationship between long noncoding (lnc) RNA-IFNG-AS1 and interferon gamma (IFN-γ) in different groups of patients with brucellosis compared to control group. In this study, associations of lncRNA IFNG-AS1 expression with secretion of IFN-γ level in Sixty patients with brucellosis, which were divided into 3 groups (acute, chronic and relapse groups), as a case group were compared with 20 subjects with negative serological tests and brucellosis clinical manifestation as a control group. In this regard, RNA were extracted from isolated peripheral blood mononuclear cells (PBMCs). LncRNA IFNG-AS1, T-box transcription factor (T-bet) and IFN-γ expressions were detected using quantitative polymerase chain reaction (qPCR). Serum level IFN-γ was assessed using enzyme linked immunosorbent assay (ELISA). The results showed that expression level of LncRNA IFNG-AS1, T-bet and IFN-γ increased significantly in all patient groups in compared to healthy subjects (P 
    Matched MeSH terms: Interferon-gamma/blood; Interferon-gamma/genetics
  6. Fulltext Role of Interferons in the Development of Diagnostics, Vaccines, and Therapy for Tuberculosis
    Chin KL, Anis FZ, Sarmiento ME, Norazmi MN, Acosta A
    J Immunol Res, 2017;2017:5212910.
    PMID: 28713838 DOI: 10.1155/2017/5212910
    Tuberculosis (TB) is an airborne infection caused by Mycobacterium tuberculosis (Mtb). About one-third of the world's population is latently infected with TB and 5-15% of them will develop active TB in their lifetime. It is estimated that each case of active TB may cause 10-20 new infections. Host immune response to Mtb is influenced by interferon- (IFN-) signaling pathways, particularly by type I and type II interferons (IFNs). The latter that consists of IFN-γ has been associated with the promotion of Th1 immune response which is associated with protection against TB. Although this aspect remains controversial at present due to the lack of established correlates of protection, currently, there are different prophylactic, diagnostic, and immunotherapeutic approaches in which IFNs play an important role. This review summarizes the main aspects related with the biology of IFNs, mainly associated with TB, as well as presents the main applications of these cytokines related to prophylaxis, diagnosis, and immunotherapy of TB.
    Matched MeSH terms: Interferon-gamma/administration & dosage; Interferon-gamma/therapeutic use
  7. Fulltext Close contact investigation of TB in high-burden, low- and middle-income countries
    Pang YK
    Malays Fam Physician, 2014;9(2):11-17.
    PMID: 25893066 MyJurnal
    Tuberculosis (TB) remains a very common disease in most of the low- and middle-income countries. As a result of high disease burden, TB control measures in these countries are usually concentrated on intensifying active disease case-finding and early treatment of infectious TB. On the contrary, in countries with low disease burden, the focus is on contact investigation to identify latently infected individuals and prophylactically treating them to prevent disease reactivation and transmission. These two strategies are deemed important for the effective TB control. Nonetheless, WHO cautions that targeted contact investigation and latent TB infection (LTBI) treatment should only be undertaken by countries that have the operational capacity/ resources and have achieved ≥ 85% treatment success rate of active TB. The screening of LTBI is further challenged by the lack of a “gold standard” test to identify and validate individuals with this condition. Tuberculin skin test (TST) is still the preferred investigation as it is cheap, widely available and validated in many trials. The sensitivity and specificity of the newer test—interferon gamma release assay (IGRA) for LTBI screening has been encouraging in low prevalence countries. However, the evidence supporting such usage remains uncertain in high burden settings. Diagnosis of LTBI should adhere to the strict criteria outlined in the guidelines to avoid misdiagnosing active TB as LTBI. The treatment of the latter involved only one or two anti-TB drugs. It has been demonstrated that in the properly conducted contact screening and LTBI treatment, chances of the emergence of multi-drug-resistant TB is very low.
    Matched MeSH terms: Interferon-gamma Release Tests
  8. The Cytokines CXCL10 and CCL2 and the Kynurenine Metabolite Anthranilic Acid Accurately Predict Patients at Risk of Developing Dengue With Warning Signs
    Jusof FF, Lim CK, Aziz FN, Soe HJ, Raju CS, Sekaran SD, et al.
    J Infect Dis, 2022 Nov 28;226(11):1964-1973.
    PMID: 35767283 DOI: 10.1093/infdis/jiac273
    BACKGROUND: The resolution or aggravation of dengue infection depends on the patient's immune response during the critical phase. Cytokines released by immune cells increase with the worsening severity of dengue infections. Cytokines activate the kynurenine pathway (KP) and the extent of KP activation then influences disease severity.

    METHODS: KP metabolites and cytokines in plasma samples of patients with dengue infection (dengue without warning signs [DWS-], dengue with warning signs [DWS+], or severe dengue) were analyzed. Cytokines (interferon gamma [IFN-ɣ], tumor necrosis factor, interleukin 6, CXCL10/interferon-inducile protein 10 [IP-10], interleukin 18 [IL-18], CCL2/monocyte chemoattractant protein-1 [MCP-1], and CCL4/macrophage inflammatory protein-1beta [MIP-1β] were assessed by a Human Luminex Screening Assay, while KP metabolites (tryptophan, kynurenine, anthranilic acid [AA], picolinic acid, and quinolinic acid) were assessed by ultra-high-performance liquid chromatography and Gas Chromatography Mass Spectrophotometry [GCMS] assays.

    RESULTS: Patients with DWS+ had increased activation of the KP where kynurenine-tryptophan ratio, anthranilic acid, and picolinic acid were elevated. These patients also had higher levels of the cytokines IFN-ɣ, CXCL10, CCL4, and IL-18 than those with DWS-. Further receiver operating characteristic analysis identified 3 prognostic biomarker candidates, CXCL10, CCL2, and AA, which predicted patients with higher risks of developing DWS+ with an accuracy of 97%.

    CONCLUSIONS: The data suggest a unique biochemical signature in patients with DWS+. CXCL10 and CCL2 together with AA are potential prognostic biomarkers that discern patients with higher risk of developing DWS+ at earlier stages of infection.

    Matched MeSH terms: Interferon-gamma
  9. A cost-effectiveness evaluation of latent tuberculosis infection screening of a migrant population in Malaysia
    Barker E, Moss J, Holmes H, Bowe C, Suryaprakash V, Alagna R, et al.
    Sci Rep, 2023 Feb 10;13(1):2390.
    PMID: 36765258 DOI: 10.1038/s41598-023-29648-z
    To estimate the costs and benefits of screening for latent tuberculosis infection (LTBI) in a migrant population in Malaysia. An economic model was developed from a Malaysian healthcare perspective to compare QuantiFERON-TB Gold Plus (QuantiFERON) with the tuberculin skin test (TST). A decision tree was used to capture outcomes relating to LTBI screening followed by a Markov model that simulated the lifetime costs and benefits of the patient cohort. The Markov model did not capture the impact of secondary infections. The model included an R shiny interactive interface to allow adaptation to other scenarios and settings. QuantiFERON is both more effective and less costly than TST (dominant). Compared with QuantiFERON, the lifetime risk of developing active TB increases by approximately 40% for TST due to missed LTBI cases during screening (i.e. a higher number of false negative cases for TST). For a migrant population in Malaysia, QuantiFERON is cost-effective when compared with TST. Further research should consider targeted LTBI screening for migrants in Malaysia based on common risk factors.
    Matched MeSH terms: Interferon-gamma Release Tests
  10. Fulltext Immunogenic Eimeria tenella glycosylphosphatidylinositol-anchored surface antigens (SAGs) induce inflammatory responses in avian macrophages
    Chow YP, Wan KL, Blake DP, Tomley F, Nathan S
    PLoS One, 2011;6(9):e25233.
    PMID: 21980402 DOI: 10.1371/journal.pone.0025233
    BACKGROUND: At least 19 glycosylphosphatidylinositol (GPI)-anchored surface antigens (SAGs) are expressed specifically by second-generation merozoites of Eimeria tenella, but the ability of these proteins to stimulate immune responses in the chicken is unknown.

    METHODOLOGY/PRINCIPAL FINDINGS: Ten SAGs, belonging to two previously defined multigene families (A and B), were expressed as soluble recombinant (r) fusion proteins in E. coli. Chicken macrophages were treated with purified rSAGs and changes in macrophage nitrite production, and in mRNA expression profiles of inducible nitric oxide synthase (iNOS) and of a panel of cytokines were measured. Treatment with rSAGs 4, 5, and 12 induced high levels of macrophage nitric oxide production and IL-1β mRNA transcription that may contribute to the inflammatory response observed during E. tenella infection. Concomitantly, treatment with rSAGs 4, 5 and 12 suppressed the expression of IL-12 and IFN-γ and elevated that of IL-10, suggesting that during infection these molecules may specifically impair the development of cellular mediated immunity.

    CONCLUSIONS/SIGNIFICANCE: In summary, some E. tenella SAGs appear to differentially modulate chicken innate and humoral immune responses and those derived from multigene family A (especially rSAG 12) may be more strongly linked with E. tenella pathogenicity associated with the endogenous second generation stages.

    Matched MeSH terms: Interferon-gamma/metabolism
  11. Influence of recombinant interferon-gamma QN the expression of MHC class I and class II antigens on four human colonic carcinoma cell lines
    Norazmi MN, Hohmann AW, Bradley J
    Malays J Pathol, 1990 Dec;12(2):89-95.
    PMID: 2129402
    The occurrence of MHC class I and class II antigens on four human colonic carcinoma cell lines and the effect of recombinant interferon-gamma (rIFNg) on the expression of these antigens was investigated by immunofluorescent flow cytometry. The concentration of rIFNg which resulted in the largest increase in expression of class I and class II antigens was determined. Changes in the amount of MHC antigen on the membrane were indicated by a shift in the mean fluorescence intensity (MFI) of the cell population. Without addition of rIFNg, the COLO 206, COLO 320F and COLO 397 cell lines were class I positive although the COLO 206 cell line expressed less class I antigen than the other two lines. The HT-29 cell line expressed only a minimal level of class I antigen. Treatment with rIFNg increased the amount of class I antigen on these cell lines 5, 1.4, 2.5 and 20 times respectively. Maximum levels of class I antigen were found two days after treatment. Class I antigen expression returned to pre-treatment levels by day 8 in all but the HT-29 cell line, which maintained its increased level following a single dose of rIFNg. All four cell lines had little or no class II antigens. Following treatment with rIFNg, DR antigen appeared on all four lines whereas DP and DQ antigens could be induced only on the 320F and 397 lines. The amount of class II antigen reached its peak two days after treatment and gradually decreased over the next 6 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)
    Matched MeSH terms: Interferon-gamma/pharmacology*
  12. Fulltext Chronic granulomatous disease--a report in two Malay families
    Mohd Noh L, Noah RM, Wu LL, Nasuruddin BA, Junaidah E, Ooi CP, et al.
    Singapore Med J, 1994 Oct;35(5):505-8.
    PMID: 7701372
    Chronic granulomatous disease (CGD) is a very rare disease whose defect lies in an abnormal intracellular killing resulting in recurrent abscesses, lymphadenitis and granuloma formation. We describe 2 Malay male infants with CGD whom we believe to be the first report of this disorder in Malays. Both children presented with recurrent abscesses, pneumoniae and hepatosplenomegaly; lymphadenopathy was also present in one of the patients. The organisms isolated were catalase positive bacteria. Both neutrophil chemiluminescence (against fungal and bacterial antigens, phorbol myristate acetate) and intracellular killing assays were severely depressed. Recognition of CGD is important as great strides have been made in the treatment of this disease which include gamma interferon therapy besides the conventional prophylactic antibacterial therapy.
    Matched MeSH terms: Interferon-gamma/therapeutic use
  13. Regulating tumor microenvironments by a lymph node-targeting adjuvant via tumor-specific CTL-derived IFNγ
    Xu X, Yi C, Feng T, Ge Y, Liu M, Wu C, et al.
    Clin Immunol, 2023 Aug;253:109685.
    PMID: 37406980 DOI: 10.1016/j.clim.2023.109685
    Inducing tumor-specific T cell responses and regulating suppressive tumor microenvironments have been a challenge for effective tumor therapy. CpG (ODN), the Toll-like receptor 9 agonist, has been widely used as adjuvants of cancer vaccines to induce T cell responses. We developed a novel adjuvant to improve the targeting of lymph nodes. CpG were modified with lipid and glycopolymers by the combination of photo-induced RAFT polymerization and click chemistry, and the novel adjuvant was termed as lipid-glycoadjuvant@AuNPs (LCpG). OVA protein was used as model antigen and melanoma model was established to test the immunotherapy effect of the adjuvant. In tumor model, the antitumor effect and mechanism of LCpG on the response of CTLs were examined by flow cytometry and cell cytotoxicity assay. The effects of LCpG on macrophage polarization and Tregs differentiation in tumor microenvironment were also studied by cell depletion assay and cytokine neutralization assay. We also tested the therapeutic effect of the combination of the adjuvant and anti-PD-1 treatment. LCpG could be rapidly transported to and retained longer in the lymphoid nodes than unmodified CpG. In melanoma model, LCpG controlled both primary tumor and its metastasis, and established long-term memory. In spleen and tumor draining lymphoid nodes, LCpG activated tumor-specific Tc1 responses, with increased CD8+ T-cell proliferation, antigen-specific Tc1 cytokine production and specific-tumor killing capacity. In tumor microenvironments, antigen-specific Tc1 induced by the LCpG promoted CTL infiltration, skewed tumor associated macrophages to M1 phenotype, regulated Treg and induced proinflammatory cytokines production in a CTL-derived IFN-γ-dependent manner. In vivo cell depletion and adoptive transfer experiments confirmed that antitumor activity of LCpG included vaccine was mainly dependent on CTL-derived IFN-γ. The anti-tumor efficacy of LCpG was dramatically enhanced when combined with anti-PD1 immunotherapy. LCpG was a promising adjuvant for vaccine formulation which could augment tumor-specific Tc1 activity, and regulate tumor microenvironments.
    Matched MeSH terms: Interferon-gamma/metabolism
  14. Fulltext Inherited human IFN-γ deficiency underlies mycobacterial disease
    Kerner G, Rosain J, Guérin A, Al-Khabaz A, Oleaga-Quintas C, Rapaport F, et al.
    J Clin Invest, 2020 Jun 01;130(6):3158-3171.
    PMID: 32163377 DOI: 10.1172/JCI135460
    Mendelian susceptibility to mycobacterial disease (MSMD) is characterized by a selective predisposition to clinical disease caused by the Bacille Calmette-Guérin (BCG) vaccine and environmental mycobacteria. The known genetic etiologies of MSMD are inborn errors of IFN-γ immunity due to mutations of 15 genes controlling the production of or response to IFN-γ. Since the first MSMD-causing mutations were reported in 1996, biallelic mutations in the genes encoding IFN-γ receptor 1 (IFN-γR1) and IFN-γR2 have been reported in many patients of diverse ancestries. Surprisingly, mutations of the gene encoding the IFN-γ cytokine itself have not been reported, raising the remote possibility that there might be other agonists of the IFN-γ receptor. We describe 2 Lebanese cousins with MSMD, living in Kuwait, who are both homozygous for a small deletion within the IFNG gene (c.354_357del), causing a frameshift that generates a premature stop codon (p.T119Ifs4*). The mutant allele is loss of expression and loss of function. We also show that the patients' herpesvirus Saimiri-immortalized T lymphocytes did not produce IFN-γ, a phenotype that can be rescued by retrotransduction with WT IFNG cDNA. The blood T and NK lymphocytes from these patients also failed to produce and secrete detectable amounts of IFN-γ. Finally, we show that human IFNG has evolved under stronger negative selection than IFNGR1 or IFNGR2, suggesting that it is less tolerant to heterozygous deleterious mutations than IFNGR1 or IFNGR2. This may account for the rarity of patients with autosomal-recessive, complete IFN-γ deficiency relative to patients with complete IFN-γR1 and IFN-γR2 deficiencies.
    Matched MeSH terms: Interferon-gamma/deficiency*
  15. L-arginine-dependent nitric oxide production of a murine macrophage-like RAW 264.7 cell line stimulated with Porphyromonas gingivalis lipopolysaccharide
    Sosroseno W, Herminajeng E, Bird PS, Seymour GJ
    Oral Microbiol. Immunol., 2004 Apr;19(2):65-70.
    PMID: 14871343
    The aim of this study was to determine nitric oxide (NO) production of a murine macrophage cell line (RAW 264.7 cells) when stimulated with Porphyromonas gingivalis lipopolysaccharides (Pg-LPS). RAW 264.7 cells were incubated with i) various concentrations of Pg-LPS or Salmonella typhosa LPS (St-LPS), ii) Pg-LPS with or without L-arginine and/or NG-monomethyl-L-arginine (NMMA), an arginine analog or iii) Pg-LPS and interferon-gamma (IFN-gamma) with or without anti-IFN-gamma antibodies or interleukin-10 (IL-10). Tissue culture supernatants were assayed for NO levels after 24 h in culture. NO was not observed in tissue culture supernatants of RAW 264.7 cells following stimulation with Pg-LPS, but was observed after stimulation with St-LPS. Exogenous L-arginine restored the ability of Pg-LPS to induce NO production; however, the increase in NO levels of cells stimulated with Pg-LPS with exogenous L-arginine was abolished by NMMA. IFN-gamma induced independent NO production by Pg-LPS-stimulated macrophages and this stimulatory effect of IFN-gamma could be completely suppressed by anti-IFN-gamma antibodies and IL-10. These results suggest that Pg-LPS is able to stimulate NO production in the RAW 264.7 macrophage cell model in an L-arginine-dependent mechanism which is itself independent of the action of IFN-gamma.
    Matched MeSH terms: Interferon-gamma/immunology; Interferon-gamma/pharmacology
  16. Fulltext Serum neopterin is elevated in patients infected with Shigella
    Singh KK, Wan-Nurfahizul-Izzati W, Ismail A
    Gut Pathog, 2010;2(1):9.
    PMID: 20727206 DOI: 10.1186/1757-4749-2-9
    Neopterin is produced by human macrophages/monocytes when stimulated with interferon-gamma. Production of neopterin is found in serum, cerebrospinal fluid (CSF) and urine of patients with infections by viruses, intracellular bacteria and parasites, autoimmune diseases, malignant tumors and patients in allograft rejection episodes.
    Matched MeSH terms: Interferon-gamma
  17. Mycobacterium tuberculosis complex in wildlife: Review of current applications of antemortem and postmortem diagnosis
    Lekko YM, Ooi PT, Omar S, Mazlan M, Ramanoon SZ, Jasni S, et al.
    Vet World, 2020 Sep;13(9):1822-1836.
    PMID: 33132593 DOI: 10.14202/vetworld.2020.1822-1836
    Tuberculosis (TB) is a chronic inflammatory and zoonotic disease caused by Mycobacterium tuberculosis complex (MTBC) members, which affects various domestic animals, wildlife, and humans. Some wild animals serve as reservoir hosts in the transmission and epidemiology of the disease. Therefore, the monitoring and surveillance of both wild and domestic hosts are critical for prevention and control strategies. For TB diagnosis, the single intradermal tuberculin test or the single comparative intradermal tuberculin test, and the gamma-interferon test, which is regarded as an ancillary test, are used. Postmortem examination can identify granulomatous lesions compatible with a diagnosis of TB. In contrast, smears of the lesions can be stained for acid-fast bacilli, and samples of the affected organs can be subjected to histopathological analyses. Culture is the gold standard test for isolating mycobacterial bacilli because it has high sensitivity and specificity compared with other methods. Serology for antibody detection allows the testing of many samples simply, rapidly, and inexpensively, and the protocol can be standardized in different laboratories. Molecular biological analyses are also applicable to trace the epidemiology of the disease. In conclusion, reviewing the various techniques used in MTBC diagnosis can help establish guidelines for researchers when choosing a particular diagnostic method depending on the situation at hand, be it disease outbreaks in wildlife or for epidemiological studies. This is because a good understanding of various diagnostic techniques will aid in monitoring and managing emerging pandemic threats of infectious diseases from wildlife and also preventing the potential spread of zoonotic TB to livestock and humans. This review aimed to provide up-to-date information on different techniques used for diagnosing TB at the interfaces between wildlife, livestock, and humans.
    Matched MeSH terms: Interferon-gamma
  18. Fulltext IFN-γ Induction of Apolipoprotein A-I Expression is Mediated by NF-κB Signalling in HepG2 Cells
    Lui Siang Tong, Hong Kin Wong, Choy Hoong Chew
    Trop Life Sci Res, 2019;30(2):1-13.
    MyJurnal
    Keradangan hati berkait rapat dengan perubahan dalam ekspresi lipoprotein dan apolipoprotein. Interferon-γ (IFN-γ), wakil tunggal jenis kedua IFN, memainkan peranan yang penting dalam memodulasi dan mempergiatkan tindak balas keradangan. Justeru itu, kajian ini direka untuk mengenal pasti kesan IFN-γ terhadap apolipoprotein A-I (APOA-I) dan penglibatan nuclear factor–kappa B (NF-κB) dalam laluan isyarat tersebut. Tindak balas rantai polymerase transkripsi berbalik kuantitatif (qRT-PCR) dan analisis blot western telah dilaksanakan untuk menguantifikasi ekspresi APOA-I dalam sel-sel HepG2 selepas dirawat dengan IFN-γ. Kajian ini menunjukkan bahawa 50 ng/mL IFN-γ merangsangkan ekspresi mRNA dan protein APOA-I. Walau bagaimanapun, pra-rawatan sel dengan inhibitor laluan isyarat NF-κB mengurangkan tahap ekspresi APOA-I. Kajian ini juga mendemonstrasikan penglibatan langsung isyarat NF-κB dalam ekspresi APOA-I akibat rangsangan IFN-γ, di mana IFN-γ meningkatkan tahap fosforilasi NF-κB p65 Ser468 dan Ser536 kepada 2.59-ganda and 1.63-ganda. Namun demikian, pra-rawatan sel dengan perencat laluan isyarat NF-κB melumpuhkan peningkatkan tersebut dan kemudian mengurangkan ekspresi APOA-I dalam sel HepG2. Sebagai rumusan, kajian ini berjaya mengenalpasti peranan isyarat NF-κB dan pengaktifan p65 Ser468 dan Ser536 sebagai pengantara IFN-γ ke atas induksi APOA-I di dalam sel-sel HepG2.
    Matched MeSH terms: Interferon-gamma
  19. Fulltext Regulation of Epigenetic Modifiers, Including KDM6B, by Interferon-γ and Interleukin-4 in Human Macrophages
    Yıldırım-Buharalıoğlu G, Bond M, Sala-Newby GB, Hindmarch CC, Newby AC
    Front Immunol, 2017;8:92.
    PMID: 28228757 DOI: 10.3389/fimmu.2017.00092
    BACKGROUND: Interferon-γ (IFN-γ) or interleukin-4 (IL-4) drives widely different transcriptional programs in macrophages. However, how IFN-γ and IL-4 alter expression of histone-modifying enzymes involved in epigenetic regulation and how this affects the resulting phenotypic polarization is incompletely understood.

    METHODS AND RESULTS: We investigated steady-state messenger RNA levels of 84 histone-modifying enzymes and related regulators in colony-stimulating factor-1 differentiated primary human macrophages using quantitative polymerase chain reaction. IFN-γ or IL-4 treatment for 6-48 h changed 11 mRNAs significantly. IFN-γ increased CIITA, KDM6B, and NCOA1, and IL-4 also increased KDM6B by 6 h. However, either cytokine decreased AURKB, ESCO2, SETD6, SUV39H1, and WHSC1, whereas IFN-γ alone decreased KAT2A, PRMT7, and SMYD3 mRNAs only after 18 h, which coincided with decreased cell proliferation. Rendering macrophages quiescent by growth factor starvation or adenovirus-mediated overexpression of p27(kip1) inhibited expression of AURKB, ESCO2, SUV39H1, and WHSC1, and mRNA levels were restored by overexpressing the S-phase transcription factor E2F1, implying their expression, at least partly, depended on proliferation. However, CIITA, KDM6B, NCOA1, KAT2A, PRMT7, SETD6, and SMYD3 were regulated independently of effects on proliferation. Silencing KDM6B, the only transcriptional activator upregulated by both IFN-γ and IL-4, pharmacologically or with short hairpin RNA, blunted a subset of responses to each cytokine.

    CONCLUSION: These findings demonstrate that IFN-γ or IL-4 can regulate the expression of histone acetyl transferases and histone methyl transferases independently of effects on proliferation and that upregulation of the histone demethylase, KDM6B, assists phenotypic polarization by both cytokines.

    Matched MeSH terms: Interferon-gamma
  20. Fulltext Cucurbitacin L 2-O-β-Glucoside Demonstrates Apoptogenesis in Colon Adenocarcinoma Cells (HT-29): Involvement of Reactive Oxygen and Nitrogen Species Regulation
    Abdelwahab SI, Hassan LE, Abdul Majid AM, Yagi SM, Mohan S, Elhassan Taha MM, et al.
    Evid Based Complement Alternat Med, 2012;2012:490136.
    PMID: 22685485 DOI: 10.1155/2012/490136
    Emerging evidence suggests that reactive oxygen (ROS) and nitrogen (RNS) species can contribute to diverse signalling pathways of inflammatory and tumour cells. Cucurbitacins are a group of highly oxygenated triterpenes. Many plants used in folk medicine to treat cancer have been found to contain cucurbitacins displaying potentially important anti-inflammatory actions. The current study was designed to investigate the anti-ROS and -RNS effects of cucurbitacin L 2-O-β-glucoside (CLG) and the role of these signaling factors in the apoptogenic effects of CLG on human colon cancer cells (HT-29). This natural cucurbitacin was isolated purely from Citrullus lanatus var. citroides (Cucurbitaceae). The results revealed that CLG was cytotoxic to HT-29. CLG increased significantly (P < 0.05) RNA and protein levels of caspase-3 in HT-29 cells when verified using a colorimetric assay and realtime qPCR, respectively. The results showed that lipopolysaccharide/interferon-gamma (LPS/INF-γ) increased nitrous oxide (NO) production inR AW264.7macrophages, whereas N(G)-nitro-L-argininemethyl ester (L-NAME) and CLG curtailed it. This compound did not reveal any cytotoxicity on RAW264.7 macrophages and human normal liver cells (WRL-68) when tested using the MTT assay. Findings of ferric reducing antioxidant power (FRAP) and oxygen radical absorption capacity (ORAC) assays demonstrate the antioxidant properties of CLG. The apoptogenic property of CLG on HT-29 cells is thus related to inhibition of reactive nitrogen and oxygen reactive species and the triggering of caspase-3-regulated apoptosis.
    Matched MeSH terms: Interferon-gamma
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